2--hydroxy-5-9-dimethyl-2-allyl-6-7-benzomorphan and 1-(1-phenylcyclohexyl)-3-methylpiperidine

The present study characterized the response of the hypothalamo-pituitary-adrenal axis after the acute administration of enantiomeric pairs of drugs that bind to phencyclidine (PCP) and sigma receptors. Rats were injected with the enantiomers of 1-(1-phenylcyclohexyl)-3-methylpiperidine (PCMP), N-allylnormetazocine (SKF 10,047), dioxadrol (dexoxadrol and levoxadrol) or pentazocine, and plasma levels of adrenocorticotropin (ACTH) and corticosterone were determined by radioimmunoassay. The effects of the enantiomers of PCMP and dioxadrol showed stereospecificity as both (+)-PCMP and dexoxadrol increased plasma levels of ACTH and corticosterone but (-)-PCMP and levoxadrol had no effect. Whereas (-)-pentazocine produced greater responses than (+)-pentazocine, the two enantiomers of SKF 10,047 did not show stereoselectivity. Although the potency of the enantiomers of PCMP and dioxadrol parallel their affinity for binding to PCP receptors, the potency of the enantiomers of pentazocine did not. These results suggest that although the stimulation of the hypothalamo-pituitary-adrenal axis by PCP and drugs with PCP-like activity might be due to interactions with PCP receptors, the effects of pentazocine also involve interactions at other sites.

Topics: Adrenocorticotropic Hormone; Analgesics; Animals; Corticosterone; Dioxolanes; Drug Interactions; Hypothalamo-Hypophyseal System; Injections, Subcutaneous; Male; Phenazocine; Phencyclidine; Piperidines; Pituitary-Adrenal System; Rats; Rats, Sprague-Dawley; Receptors, sigma; Stereoisomerism; Sympathomimetics

The potency of a series of opioid and non-opioid psychotomimetic drugs to inhibit the specific binding of [3H]PCP and (+)-[3H]SKF-10,047 to rat cerebral cortical membranes was examined. (+)-PCMP, the 3-methylpiperidino analog of PCP, was a potent inhibitor of the specific binding of both ligands. All of the other 12 compounds examined, however, displayed a 3-277-fold selectivity for either [3H]PCP or (+)-[3H]SKF-10,047 binding. These results suggest that although these opioid and non-opioid psychotomimetics bind to both sites, most have significantly different affinities. The binding sites for [3H]PCP appear to be distinct from the 'sigma' binding sites labeled with (+)-[3H]SKF-10,047.

Topics: Animals; Binding Sites; Binding, Competitive; Cerebral Cortex; Male; Phenazocine; Phencyclidine; Rats; Rats, Inbred Strains; Receptors, Neurotransmitter; Receptors, Phencyclidine; Stereoisomerism